CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Subjects should be 18-70 years old.
2. Subject has adequate performance status as defined by ECOG score of≤ 2.
3. Expected life expectancy is no less than 12 weeks.
4. Subjects must have histologically or cytologically confirmed unresectable, recurrent and / or metastatic hepatocellular carcinoma (HCC). And tumor tissues are measured positive for B7H3 expression.
5. Child-Pugh A, B grade.
6. Blood routine:

   white blood cell count≥ 2.5 × 10\^9 / L; hemoglobin≥ 9 g/dL; platelet count≥ 50 × 10\^9 / L; lymphocyte proportion≥ 15 %;
7. Adequate organ function. Patients' main organs ( heart, lung, liver, kidney, etc. ) function well:

   ALT and AST≤ 5 × ULN; ALB≥ 30 g/L； Total bilirubin≤ 2.5 × ULN； Serum creatinine\< 220μmol/L; Indoor oxygen saturation ≥ 95 %; Left ventricular ejection fraction≥ 40%;
8. No allergic reaction to contrast agents.
9. Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production.
10. Patients or their legal guardians voluntarily participate in and sign the informed consent form.

Exclusion Criteria:

1. The subject is a pregnant or lactating woman.
2. The subjects have infectious diseases (such as HIV, syphilis, active tuberculosis, etc.);
3. The subject has active infection or coagulation dysfunction.
4. Subjects with previous hepatic encephalopathy.
5. The subject is on anticoagulation or antiplatelet therapy.
6. The subject is an organ transplant or waiting for transplant.
7. Subjects with mental or psychological diseases who cannot cooperate with treatment and efficacy evaluation.
8. The subjects are highly allergic or have a history of severe allergies.
9. The subject has received chemotherapy/radiotherapy within the past 4 weeks.
10. The subject has a history of cellular immunotherapy or antibody therapy.
11. The subject is receiving systemic hormone therapy.
12. Subjects with systemic infection or severe local infection requiring anti-infection treatment.
13. The subject has dysfunction of important organs such as heart, lung, brain, liver, and kidney.
14. The subject is participating in other clinical research.
15. The doctor believes that there are other reasons not to be included in the treatment.
16. Unwilling or unable to provide consent/assent for participation in the study.

主要终点：Safety of fhB7H3.CAR-T cells · Adverse events, including the type, frequency, severity and duration, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed. · 1 month；Objective response of fhB7H3.CAR-T cells · Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete Response (CR): disappearance of all target lesions, all target nodules must be reduced to normal size (short axis \<10 mm). Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive. Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. · 1 month
次要终点：In vivo persistence of fhB7H3.CAR-T cells

• fhB7H3.CAR-T cells · EXPERIMENTAL · In phase I study , 9 enrolled patients diagnosed with advanced liver cancer will receive one-time transhepatic arterial infusion of fhB7H3.CAR-Ts at the doses of 1×10\^6/kg, 3×10\^6/kg and 5×10\^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts.

This is single center, open-label phase I/II, non-randomized study which will enroll patients with recurrent advanced hepatocellular carcinoma to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T in treating hepatocellular carcinoma.